title: Enzymatically degradable thermogelling poly(alanine-co-leucine)-poloxamer-poly(alanine-co-leucine).
abstract: In the search for an enzymatically degradable thermogelling system, we are reporting poly(alanine-co-leucine)-poloxamer-poly(alanine-co-leucine) (PAL-PLX-PAL) aqueous solution. As the temperature increased, the polymer aqueous solution underwent sol-to-gel transition at 20-40 °C in a polymer concentration range of 3.0-10.0 wt %. The amphiphilic polymers of PAL-PLX-PAL form micelles in water, where the hydrophobic PALs form a core and the hydrophilic PLXs form a shell of the micelle. FTIR, circular dichroism, and (13)C NMR spectra suggest that the α-helical secondary structure of PAL is preserved; however, the molecular motion of the PLX significantly decreases in the sol-to-gel transition range of 20-50 °C. The polymer was degraded by proteolytic enzymes such as matrix metalloproteinase and elastase, whereas it was quite stable against cathepsin B, cathepsin C, and chymotrypsin or in phosphate-buffered saline (control). The in situ formed gel in the subcutaneous layer of rats showed a duration of ∼ 47 days, and H&E staining study suggests the histocompatibility of the gel in vivo with a marginal inflammation response of capsule formation. A model drug of bovine serum albumin was released over 1 month by the preset-gel injection method. The thermogelling PAL-PLX-PAL can be a promising biocompatible material for minimally invasive injectable drug delivery.
authors.affiliation: Department of Chemistry and Nano Science, Ewha Womans University, Daehyun-Dong, Seodaemun-Ku, Seoul 120-750, Korea.
authors.forename: Hyo Jung
authors.initials: HJ
authors.lastname: Moon
authors.forename: Bo Gyu
authors.initials: BG
authors.lastname: Choi
authors.forename: Min Hee
authors.initials: MH
authors.lastname: Park
authors.forename: Min Kyung
authors.initials: MK
authors.lastname: Joo
authors.forename: Byeongmoon
authors.initials: B
authors.lastname: Jeong
mesh_terms: D002401:Cathepsin B / Q000378:metabolism*; D002942:Circular Dichroism; D006868:Hydrolysis; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D008855:Microscopy, Electron, Scanning; D015394:Molecular Structure; D020442:Poloxamer / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D008823:Micelles; D011108:Polymers; D011506:Proteins; D020442:Poloxamer; D002401:Cathepsin B